RAD51G135C和XRCC3C241T基因型与急性髓系白血病疗效及预后相关性研究  

Polymorphisms of RAD51G135C and XRCC3C241T genes and correlations thereof with prognosis and clinical outcomes of acute myeloid leukemia

作　　者：刘亮[1] 杨琳[1] 张悦[1] 徐泽锋[1] 于明华[1] 王建祥[1] 肖志坚[1] 

机构地区：[1]中国医学科学院北京协和医学院血液学研究所、血液病医院、实验血液学国家重点实验室,天津300020

出　　处：《中华医学杂志》2008年第6期378-382,共5页National Medical Journal of China

基　　金：新世纪优秀人才支持计划基金资助项目（NCET-05-0173）,国家“863”计划基金资助项目（2006AA02A405）

摘　　要：目的探讨同源重组修复基因RAD51G135C和XRCC3C241T多态性位点基因型与急性髓系白血病（AML）疗效及预后的关系。方法AML患者372例，用聚合酶链反应-限制性内切酶片段长度多态性（PCR-RFLP）方法分析RAD51G135C、XRCC3C241T基因型，用多重PCR方法检测GSTT1和GSTM1基因。比较不同基因型患者的诱导治疗完全缓解（CR）率、总体生存期、无复发生存期及不良反应。结果（1）在第一疗程诱导治疗过程中，XRCC3C241T基因型与AML伴t（15；17）／PML-RARα患者的早期病亡率有显著相关性（OR=8，750，P=0．046）。XRCC3C241T、RAD51G135C分别与GSTT1、GSTM1联合存在变异时，非M3患者诱导缓解时CR率明显降低，（P=0.028）。（2）XRCC3C241T、RAD51G135C的基因型影响AML患者的平均生存期及平均无复发生存期：RAD51G135C、GSTT1基因存在双变异及联合GSTM1基因均变异时，非M3的AML的生存期（OS）显著缩短（P〈0．05）。XRCC3C241T与GSTT1联合分析，双基因均野生型M4EO、M2患者的无复发生存期（RFS）明显长于双变异型患者的RFS期（均P〈0．05）。XRCC3C241T、GSTT1、GSTM1基因同时变异的M2患者的RFS期（10、0个月）明显短于3个基因野生型患者（64．2个月，P〈0．005）。RAD51G135C、GSTT1双基因变异M4EO患者的平均RFS期明显缩短（P=0．047）。（3）XRCC3C241T、RAD51G135C基因型与第一疗程诱导治疗过程中的不良反应（包括白细胞数、恶心呕吐、脱发和血尿）有明显的相关性（均P〈0．05）。结论XRCC3C241T、RAD51G135C单独或与GSTT1，GSTM1基因型联合变异，与AML患者第一疗程诱导治疗CR率、预后及毒副反应均有显著相关性，XRCC3C241T、RAD51G135C基因型的检测有助于指导AML患者个体化治疗方案的制定。Objective To investigate the impacts of RAD51G135C and XRCC3C241T genotypes on the response, adverse effects, and prognosis of acute myelocytic leukemia（AML）. Methods RAD51G135C, XRCC3C241T, GSTT1, and GSTM1 genotypes were analyzed in 372 patients with AML, 226 males and 146 females, by PCR-RFLP or PCR. The Complete remission （CR） rate, adverse effects, overall survival （OS） , and relapse-free survival （RFS） were compared among the groups with different genotypes. Results （1） During the induction chemotherapy, XRCC3C241T polymorphic allele was significantly associated with the shorter survival of the AML patients with t （ 15 ; 17）/PML-RARα （ OR = 8. 750, P = 0. 046）. Among the non-Ms patients, the complete remission （CR） rate of those with double RAD51G135C and GSTT1 wild genotypes was 71.6 %, significantly higher than that of those not with double RAD51G135C and GSTT1 wild genotypes （54.4 %, P =0. 028）. （2）The OS of the non-Ms AML patients with double RAD51G135C and GSTT1 wild genotypes was （39.1 ± 7.1 ） months, significantly longer than those with double variant types [ （22.4 ±3.2） months, P =0. 042]. The relapse-free survival （RFS） of the M4EO and M2 patients with double XRCC3C241T and GSTT1 wild type genotype were 48.3 months and 56.5 months, both significantly longer than those of the patients with double variant genotypes （28.8 months and 10.0 months respectively, both P 〈0.05）. The OS of the M2 patients with triple RAD51G135C, GSTT1, and GSTM1 variant genotypes was （22.4 ± 3.2） months, signifieantly shorter than those with triple RAD51G135C, GSTT1, and GSTM1 wild genotypes [ （39.1 ± 7. 1 ） months, P = 0. 042]. The RFS of the M2 patients with triple RAD51G135C, GSTT1 ,and GSTM1 variant genotypes was 10. 0 months, signifieantly shorter than that of the patients with triple RAD51G135C, GSTT1 ,and GSTM1 wild genotypes （64.2 months, P =0.015）. （3） The risk levels of neutropenia, nausea and vomiting, and alopeeia of the patients with

关 键 词：白血病 粒细胞 急性 XRCC3基因 RAD51基因 

分 类 号：R686[医药卫生—骨科学]